Derivatives of 2:3-dihydro-4-methylthieno(3:2-c) quinoline and preparation thereof



Patented Aug. 25, 1953 it DERIVATIVES OF 2:3-DIHYDRO-4-METHYL- THIENO(3:2-c) QUINOLINE AND PREPARA- TION THEREOF Helmut Timmler, Hans Andersag, and Stephan Breitner, Wuppertal-Elberfeld, Germany, as-

slgnors to Schenley Industries, Inc., New York, N. Y., a corporation 'of Delaware No Drawing. Application May 28, 1951, Serial No.

228,762. In Germany May 27, 1950 7 Claims. (or. 260288) This invention relates generally to the syn- 04mg thesis of novel organic chemical compounds and, more particularly, it is concerned with the syn thesis of polynuclear"heterocyclic compounds useful in chemotherapyfi r NH This application is related to our copending application Serial No. 228,761 filed May 28, 1951, H as a companion application for the sulfur isologs of the same series of; compounds. These com .011; pounds have interesting and useful properties N making them suitable for use in chemotherapy particularly as analgesics, stimulants and as amoebicicles. This application is similarly related to our copending application Serial No. 228,765 also filed on May 28, 1951.

The novel compounds of this invention may be regarded as derived from 2 :3-dihydro-4-methylthieno (3:2-c) quinoline, which is represented by the formula:

SMCHI I a, p p I having a bridging group, linked to one pair of adjacent positions of the bz nucleus, which comp a prises a secondary amino group ma chain with ually and malntaimng the reaction mixture at a two carbon atoms linked by a double bond, which temperature of about upwards to r 1 boiling point of the reaction mixture. The demay be resented 0 mu sired final product may be shaken out with ether 1 p and recovered from the ethereal extract in the NH- "usual manner.

The two step reaction involving initial treatment of the Schiffs base with phosphorus oxychloride, isperiormed in a liquid hydrocarbon Compou ds of t is in'ventionlmay be prepared 40 action of this dichloro intermediate product with easily y treatment Of a correspondingly Substithiourea, is performed in a lower alkanol, such tuted Schiffs-base type compound, derived from as than l,

the condensation of a-acetyl-butyrolactone with To "f cilit t b tte understanding of th a suitably substituted aniline. When the Schifis b t tt of t invention, examples m base is treated with phosphorus pentasulfide, or trafi gth synthesi of pecific compounds hereh it i treated with phosphorus oxychloride with follow, but it is clearly to be understood that.

followed by reaction with thiourea, the desired these examplesare provided by way ofillustrafinal product is obtained, These reactions may tion merelmand arenot to be construed as being;

be represented as follows: limit ations upon thescopeof theinvention.

3 Example 1 O--'CH1 (EHaCHaCl Aboutldpartsnf the Schiffs base type compound, prepared from 3-aminocarbazole and aacetyl-butyrolactone, are heated under reflux with It parts of 'phosphorus oxychloride for 2 hours, then the excess phosphorus oxychlor-ide is evaporated in vacuo and the residue is decomposed with ice and ammonia. The reaction product is taken up with methylene chloride; the solvent is evaporated, and residue remaining is recrystallized from ethanol. The compoundrepresented by Formula V above is thus obtained as yellowish crystals, melting at 215 C. About 33 parts of this dichloro compound'are boi'ledwith 8 parts of thiourea in 300 parts of ethanol for one hour. The precipitated yellow material which fdrms'is thef hydrochforide of the"com pound represented-byj-Formula' VIabove. It is removed by filtration; dissolvedin a largequam tity of hot water, and-the free base is "precipitated by addition'of ammonium hydroxide. After recrystallization from ethanol; the'purified product is obtained as prismatic needles, melting at 2&3 C.

Example 2 The same final product (.VI) of Example-l may be obtained" directly by treatment of. the Schifts base starting material (IV) with phosphorus coal, thenlprecipitated by addition of ammonium hydroxide solutionand crystallized from li'groin.

Example 3 VII o--om O= H: C

i015: N \POCI: H \l p (VIII) base starting material VII with phosphorus pentasulfide as described in Example 2.

Having thus described the subject matter of this invention, what it is Letters Patent is:

1. As new compositions of matter, chemical compounds represented by the formula:

s ore formula 2. A compound defined in claim 1 wherein the bridging group is across the 8:9 positions.

3. A compound represented by the formula desired to secure by a 4. A compound represented by the formula:

5. Process for the preparation 01' organic chemical compounds represented by the formula:

that comprises treating with phosphorus oxychloride, at an elevated temperature and while dissolved in a liquid hydrocarbon solvent, a compound represented by the formula:

whereby a dichloro-compound is formed, represented by the formula:

OHz.OH,. 01

reacting this dichloro-compound, at an elevated temperature and while dissolved in a lower alkanol, with thiourea to form the desired final product, and recovering this product from the reaction mixture.

6. Process for the preparation of organic chemical compounds represented as follows:

CHrCHzCl LC H3 N H characterized in that the Schiifs base starting material is refluxed in a liquid hydrocarbon solvent with phosphorus oxychloride to form the indicated dichloro-compound, and this dichlorocompound is converted to the indicated final product by heating it, while dissolved in a lower alkanol, with thiourea.

7. Process for the preparation of organic chemical compounds represented as follows:

characterized in that the Schiifs base starting material is refluxed in a liquid hydrocarbon solvent with phosphorus oxychloride to form the indicated dichloro-compound, and this dichlorocompound is converted to the indicated final product by heating it, while dissolved in a lower alkanol, with thiourea.

HEIMUT TIMMLER.

HANS ANDERSAG.

STEPHAN BREITNER.

No references cited. 

1. AS NEW COMPOSITIONS OF MATTER, CHEMICAL COMPOUNDS REPRESENTED BY THE FORMULA: 